Neoplasms

All Conditions

Thoracic Neoplasms

Thoracic cancer patient s/p scheduled RT will be arranged to undergo Thallium-201 Myocardial Perfusion Study. The scheduled RT will be arranged by clinical judgments of radiation-oncologists. All of the patients will receive myocardial SPECT before and after the scheduled RT.

One-day Tl-201 stress/rest MPI protocol with pharmacological stress, as daily practice will be applied. CZT camera with multipinhole collimator and stationary detectors scan heart simultaneously. A 10% symmetrical energy window at 140 keV was used. Electrocardiogram-gated scans will be applied. Perfusion images were reconstructed in standard axis and polar maps of the left ventricle were obtained. Scans from CZT was analyzed in consensus by two experienced readers blinded to any information on patient identification. The software package Myovation for Alcyone, QGS and QPS were used for quantitative analysis of MPI polar maps. Automated analysis to determine ejection fraction.

Thallium-201 Myocardial Perfusion Study

Shan-Ying Wang, M.D.

Background:

Chemoradiation is an important treatment strategy of locally advanced inoperable or unresectable disease. Radiation dose is an independent predictor of a pathological response. In addition, chemotherapy has further impact on the aspect of outcome. Improvements in local treatment delivery are needed to facilitate dose escalation and to minimize toxicity. There have been sequential improvements in tumor localization, radiation planning and delivery over the years. Helical tomotherapy nowadays provides the most precise data on radiotherapy (RT) dose delivered to thoracic malignancies, and allows greater sparing of the heart from doses associated with increased complications. However, heart disease shows a wide spectrum of pathologies, and multiple risk factors related. The damage of the myocytes may lead to not only myocardial perfusion defects, but also in functional deterioration, or even in biomarkers.

Since the impact of radiation-induced heart injury in patients with thoracic malignancies (including esophageal cancer, lung cancer, et al) is poorly documented, we try to delineate of RT-related cardiac effects and clinical impacts.

Objective:

This study aims to investigate the correlation of post-tomotherapy cardiovascular effects with myocardial perfusion and cardiac functional studies.

Methods:

The study plans to enroll thoracic cancer patients who will undergo local RT after complete staging. Patients will receive global risk scoring assessment (Framingham Risk Score, FRS), blood sampling for basic biochemistry, inflammatory biomarker, and myocardial perfusion image (MPI) at the time points of before and after RT. The results of MPI will be analyzed in qualitative visual interpretation of perfusion patterns, and functional quantitative data for cardiac functional parameters as well. The patients will be regular followed-up in CV OPD, following clinical judgement and guideline. The association between baseline and follow-up MPI, biomarker and clinical presentation will be further investigated.

Expected results:

We will obtain myocardial perfusion visual qualitative data in patients who received locoregional RT, respectively. These results will help in the understanding of pathophysiology, clinical management and follow-up of suspected RT-related heart disease.

The risk of RT-related heart disease is now well recognized but the underlying mechanisms of its initiation and progression, and the roles played by microvascular damage, fibrosis and atherosclerosis remain unclear. Studying RT-related heart disease have demonstrated that irradiation affects cardiac structure and microvascular function in a dose and time-dependent manner, with substantial damage after intermediate and high dose irradiation, and minor alterations after lower doses. Not only structural changes but also functional deterioration was noted. Studies disclosing that incidence of post 3D-RT perfusion defect is in approximately 40%, and the patients had volume-dependent perfusion defects within 2 years of RT.

To better evaluation of the RT-related heart disease, we plan to initiate a prospective study trail that takes advantage of recent technical advances in tomotherapy, and new Cadimium-Zinc-Telluride (CZT) cardiac camera.

- Estimated Case Number: 100 patients will be enrolled in the study.

1. Patients with thoracic cancer will be transferred to CV OPD for initial cardiovascular risk factors assessment, before starting radiation therapy.
2. Past history, family history, basic lab data and Framingham cardiovascular risk assessment will be applied. After approaching risk stratification, patients who were classified as intermediated to high risk need further work-up. Who needs to undergo myocardial perfusion study will be enrolled in the study before further RT course.
3. All enrolled subjects provide basic demographic data and sign informed consents.
4. Myocardial perfusion images with Tl-201 and CZT camera will be performed in nuclear medicine department of FEMH, completing baseline evaluation before RT.
5. The patients received scheduled treatment plan, including RT.
6. Follow-up CV OPD based on clinical decision and guideline: blood biochemistry and inflammation marker, CV risk scores. Further work-up would be indicated if functional status deterioration or aggravated symptoms.
7. Post-therapeutic myocardial perfusion study 12 months after first CV OPD visit.
8. Comparing the clinical follow-up data between groups, including global functional assessments, blood sampling data, myocardial perfusion scan, and quantitative cardiac functional parameters.

Blood sampling Peripheral blood will be drawn for measurements of blood glucose, lipid profile, and circulating biomarker of CRP. The genomic tests will not be involved in the study.

Myocardial perfusion study-for quantitative functional parameters, qualitative and quantitative myocardial perfusion scan. Patients referred for SPECT MPI for evaluation of CAD underwent a 1-day Tl-201 stress/rest MPI protocol, as daily practice in FEMH. Pharmacological stress was induced by standard dipyridomale infusion. Tl-201 of 2 mCi was injected after 7 min of induced stress. The software package Myovation for Alcyone (GE Healthcare), QGS and QPS were used for quantitative analysis off MPI polar maps using a 17-segment model for the left ventricle. Automated analysis of gated acquisitions from high-dose (rest) scans was performed to determine left ventricular ejection fraction (LVEF).

Integrated clinical information, follow-up and nuclear medicine cardiac scans performed in the time points of before \& after RT will be collected and analyzed.

Monitoring Radiobiological Effects in Thoracic Malignancy by Using Myocardial Perfusion Scan

Monitoring Radiobiological Effects in Thoracic Malignancy by Using Myocardial Perfusion Scan: Correlation Between Radiotherapy Dose Distribution, Myocardial Perfusion, Cardiac Function, Serum Biomarkers and Clinical Prognosis.

By literature reviewing, cardiovascular functional status in patients received helical tomography has not been fully investigated yet. And the post-therapeutic heart disease tends to show a wide spectrum of pathologies and multiple risk factors. We will monitor risk factors of underlying disease, family history, metabolism, biomarkers, myocardial perfusion defect patterns, and cardiac functional parameters, in order to delineation of RT-related effects and clinical prognosis.

Far Eastern Memorial Hospital

Behaviors and Mental Disorders

Nervous System Diseases

Rare Diseases

Cognitive Dysfunction

Brain Neoplasms

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Tumor, Childhood

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Lithium Carbonate

Antidepressive Agents

Enzyme Inhibitors

Lithionit 42 mg (lithium sulphate, 6 mmol), start dose 1x1, then slow dose escalation using therapeutic drug monitoring (TDI) to establish a target serum level of 0.5-1.0 mmol/liter.

Identical looking placebo (white round tablet, 10 mm diameter) will be dose escalated and monitored the same way as lithium, with sham values guiding the dosing.

Lithium

White round tablet, 10 mm. Identical to experimental drug (lithium)

Placebo

Klas Blomgren, MD, Professor

Gustaf Hellspong, MD, PhD Student

Gustaf Hellspong, MD

Klas Blomgren, MD, professor

Randomized, placebo-controlled, double-blinded, parallel group clinical trial to investigate if 6 months of oral lithium tablets (S-lithium 0,5-1,0 mmol/l) will prevent cognitive decline after brain radiotherapy in pediatric brain tumor survivors.

Primary outcome measure is Processing Speed Index (PSI) 2 years after start of study treatment.

Late-appearing cognitive side effects after brain radiotherapy is a potential disabling condition in pediatric brain tumor survivors. It can have profound negative effects on education, career options and quality of life. There is no current interventional drug treatment to prevent this intellectual impairment after brain tumor treatment.

Primary objective:

To assess the efficacy of lithium treatment (up to 7 years) after brain radiotherapy (both whole brain and focal) for central nervous system malignancy in preventing late-appearing cognitive processing speed impairment in children aged 5 or older.

Secondary objectives:

* To assess the efficacy of lithium treatment through evaluation of other neuropsychological/quality of life test scores.
* To assess the efficacy of lithium treatment through evaluation of radiological findings after lithium treatment using Magnetic Resonance Imaging (MRI) of the brain.

Exploratory objectives:

To explore the feasibility, safety and tolerability of lithium treatment in this patient group, using side effect forms/adverse events (AE) reporting and laboratory measures.

Randomization is based on whether or not the study participant had received radiotherapy to the whole brain (CSI) or only part of it (focal irradiation). Within each of these two arms there is a predetermined block randomization with a 2:1 lithium:placebo ratio.

Identical-looking placebo is used. S-lithium levels are masked by using a separate lab service and sham values for placebo group.

Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy

* Number of potentially eligible patients identified
* Number of patients screened
* Number of patients randomized
* Number of patients completing the study per protocol
* Number of patients terminating study during IMP treatment period (6 months).
* Number of patients terminating study during follow-up period (up 5 years post IMP treatment)

* Description of reason why eligle patient declined screening
* Description of reason why screened patient was not randomized/included
* Description of reason(s) for early study termination.

Duration of IMP treatment, measured in total number of days where IMP was taken

* Numbers of IMP dose reductions
* Number of IMP temporary stops

* Descriptions of reason(s) for IMP dose reductions
* Descriptions of reason(s) for IMP temporary stops
* Descriptions of reason(s) for IMP premature (before per protocol) permanent stop.

* Number of target serum concentration measurements within target range (0.5-1.0 mmol/liter) divided by total number of measurements.
* Number of target serum concentration measurements above target range (0.5-1.0 mmol/liter) divided by total number of measurments
* Number of target serum concentration measurements below target range (0.5-1.0 mmol/liter) divided by total number of measurments

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

Cognitive processing speed. Normed score min 45, max 155. Higher = better.

* Verbal Comprehension Index (VCI)
* Visual Spatial Index (VSI)
* Fluid Reasoning Index (FRI)
* Working Memory Index (WMI)

Normed score min 45, max 155. Higher = better.

Motor speed / manual dexterity. Unit: time in seconds to complete all pegs. Lower=better.

Visual motor integration. Normed score min 1, max 19. Higher = better.

Sustained attention. Multiple T-scores, min 0, max 80. Higher = better.

Executive function and inhibition, age 8 years and above. Normed score min 1, max 19. Higher = better.

Executive function and inhibition. Normed score min 1, max 19. Higher = better.

Executive function and inhibition, age below 8 years. Normed score min 1, max 19. Higher = better.

Health related quality of life. Score min 0, max 100. Higher=better.

Loneliness scale. Score min 3, max 9. Lower = better.

Psychosocial strengths and difficulties. Score min 0, max 40.

Executive function. Score min 20, max 80.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Monitoring Radiobiological Effects in Thoracic Malignancy by Using Myocardial Perfusion Scan	NCT01913769	Thoracic Neopla... Late Effect of ...	Thallium-201 My...	20 Years - 80 Years	Far Eastern Memorial Hospital
Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy	NCT06051240	Cognitive Impai... Cognitive Decli... Radiotherapy Si... Radiotherapy; C... Brain Tumor Memory Impairme... Late Effect of ...	Lithium Placebo	5 Years -	Region Stockholm
Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy	NCT06051240	Cognitive Impai... Cognitive Decli... Radiotherapy Si... Radiotherapy; C... Brain Tumor Memory Impairme... Late Effect of ...	Lithium Placebo	5 Years -	Region Stockholm
Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy	NCT06051240	Cognitive Impai... Cognitive Decli... Radiotherapy Si... Radiotherapy; C... Brain Tumor Memory Impairme... Late Effect of ...	Lithium Placebo	5 Years -	Region Stockholm
Monitoring Radiobiological Effects in Thoracic Malignancy by Using Myocardial Perfusion Scan	NCT01913769	Thoracic Neopla... Late Effect of ...	Thallium-201 My...	20 Years - 80 Years	Far Eastern Memorial Hospital

Spots Global Cancer Trial Database for late effect of radiation